Therapeutic vascular occlusions (embolizations) are techniques used to treat certain pathological conditions in situ and involve the injection of an embolic material into the vessel of concern. For example, blood vessels which nourish a tumor are deliberately blocked by injection of an embolic material into the vessel. Notably in the case of tumors, vascular occlusion can suppress pain, limit blood loss on the surgical intervention to follow embolization, or even bring on a tumoral necrosis and avoid the operation.
In the case of vascular malformations, such as AVM or arteriovenous fistulas, vascular occlusion enables the blood flow to the tissues to be normalized, aids in surgery, and limits the risk of hemorrhage. In hemorrhagic processes, vascular occlusion produces a reduction of flow, which promotes cicatrization of the arterial opening(s).
Embolization can be used in the treatment of uterine fibroids, postpartum and/post-caesarian bleeding, post-surgical vaginal bleeding, the prevention and/or treatment of hemorrhage from ectopic pregnancy, prophilatically prior to myomectomy and in obstetrical patients at high risk for bleeding, such as those patients with placenta previa, placenta accreta, and twin fetal death. Embolization can also be used to stop uncontrolled bleeding, or to slow bleeding prior or during surgery, and for sealing endoleaks into aneurysm sacs. Each of the above diseases or disorders is within the scope of the invention.
Furthermore, depending on the pathological conditions treated, drug delivery and/or therapeutic embolization can be carried out for temporary as well as permanent objectives.
Embolization is carried out generally by means of catheters making it possible to position particulate occlusion agents (emboli) in the circulatory system. For precise positioning some visual control is required. Therefore it is desired to use an embolic material that is suitably labeled by the addition of a contrast agent. For reducing the interference with the catheters, solid embolic materials are preferred over liquid embolic materials, which can stick to the catheter. Microspheres have been used as a suitable solid material in passive embolization, i.e., mechanical occlusion of particular vessels or sites in vivo.
A further advantage of microspheres is their potential as agents for drug delivery or for active embolization therapy. In drug delivery, the microspheres are used as a carrier for a drug/therapeutic or active agent, which is then released from the microspheres at the desired site in vivo, irrespective of whether mechanical blockage is desired or not. In active embolization therapy, the microspheres have a dual function: mechanical blockage (embolization) and highly localized, in situ delivery of a therapeutic agent. This agent can be used, for example, in the treatment of tumors with a chemotherapeutic or radiotherapeutic agent. This type of regional therapy can localize treatment at the site of the tumor. Potential site effects and damage to healthy tissue can thus be reduced, in particular when using cytotoxic chemotherapeutic or radiotherapeutic agents. Regional administration of the drug/agent (by active embolization or drug delivery) has the further advantage of increasing peak drug concentrations to the target tissue. This is not only advantageous for the administration of chemotherapeutic or radiotherapeutic agents but also for the administration of, for example, chemotherapeutic or pain relieving drugs.
However, the type of contrast agent loaded onto the microspheres has been found to alter the properties of the microspheres, such as reducing swellability of swellable materials, capacity to load additional components, such as a drug, or suitability to be injected by a catheter. Therefore, it is advantageous to provide microspheres suitable for embolization that are not only labeled but that are furthermore still capable of adsorbing or otherwise carrying a drug. Similarly, microspheres of the invention are useful for delivery of drugs or other therapeutics to particular cells, tissues or organs.
Thus, there is a demonstrated need for the further development of microspheres comprising a contrast agent, a drug, and/or another therapeutic agent which optionally can swell to sizes greater than their initial size. Therefore, it is an object of the present invention to provide contrast agent-containing microspheres with superior capacities for drug loading and/or delivery. It is another object of the invention to provide contrast agent-containing microspheres that have superior swelling properties. It is a further object of the invention to provide contrast agent-containing microspheres that have a hydrogel-like behavior. The contrast agent-containing microspheres can be suitable in active embolization therapy and/or in drug-delivery, and, in particular, for the treatment of angiogenesis-dependent diseases and/or relief of tumor-related pain.